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Main checkpoints of the JNK-MAPK pathway using the Boolean network simulation following HTLV-1-associated leukemia
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  • Shayan Mardi,
  • Arash Letafati,
  • Amin Hosseini,
  • Reza Faraji,
  • Parastoo Hosseini,
  • Sayed-Hamidreza Mozhgani
Shayan Mardi
Arak University of Medical Sciences
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Arash Letafati
Tehran University of Medical Sciences
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Amin Hosseini
Alborz University of Medical Sciences
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Reza Faraji
University of Tehran
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Parastoo Hosseini
Tehran University of Medical Sciences
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Sayed-Hamidreza Mozhgani
Alborz University of Medical Sciences

Corresponding Author:[email protected]

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Abstract

The c-Jun N-terminal kinase (JNK) pathway is a signal transduction pathway that plays a critical role in cell growth and survival. Its dysregulation is related to various cancers, including Adult T-cell Leukemia/Lymphoma (ATLL), an aggressive peripheral T-cell malignancy due to infection with the Human T-cell lymphotropic virus type 1 (HTLV-1). ATLL currently has no vaccine or definitive treatment. This research aimed to identify the JNK-MAPK pathway checkpoints to suggest possible therapeutic targets using Boolean network analysis. First, the involved genes and their interactions in the JNK pathway were identified and mapped. Next, a boolean network analysis was performed using the R programming language, which suggested Protein kinase B (AKT) and MAP kinase phosphatase (MKP) for further evaluation. Finally, to confirm the effect of these two genes, a case-control study was conducted among ATLL patients and healthy individuals. The quantitative reverse transcription polymerase chain reaction (qRT-PCR) method showed a statistically significant decrease in the expression of AKT and MKP in ATLL patients compared to the normal group. This highlights the potential role of these two genes as therapeutic targets in ATLL.